Thursday, 17 January 2008

An interesting brain teaser

A patient was admitted to another institution with fever. She was a poor historian due to a background of dementia. Hence, obtaining a thorough history was not possible and moreover, the patient did not complain of any problems.

The fever had been going on for several weeks and was not associated with chills or rigors.

There was no respiratory,abdominal or urinary symptoms. There were no complaints of joint problems or skin problems. There was no facial or ear pain. There was no history of dental work or recent gastrointestinal endoscopic examinations.

There was no history of other people developing such fever in her nursing institution.

Her previous history included dementia, type 2 diabetes, hypertension and hyperlipidaemia.

She took voglibose, amlodipine and atorvastatin only.

She had no relevant family history of note.

On examination

Fever was 39 degrees and the patient looked well. She had digital clubbing.No splinter haemorrhages or Janeway lesions.

CVS: pulse 100 per minute, regular, BP 110/70mmHg, JVP elevated to her ears, heart sounds normal.Peripheral oedema ++

RESP: Respiratory rate 16/minute, Sats 95% on room air, tracheal central, no lymph nodes, bilaterally decreased air entry at both bases posteriorly.

ABDO: Soft, non-tender, no organomegaly, normal bowel sounds,no renal angle tenderness or suprapubic tenderness, rectal examination normal.

MUSC: No joint pain or swelling, no evidence of DVT.

Examination of the urine in the draining Foley catheter revealed murky fluid.
The catheter had been in situ for several weeks.


The impression was of a urinary tract infection causing the fever and grossly abnormal urine.

There was also evidence of chronic heart failure


The urine examination revealed 3+ bacteria and 3+ fungi.

It was initially considered that the fungi were present due to long term catheter placement. However, the bacterial component of the urine was treated initially with meropenem, then ceftriaxone and finally with vancomycin without a specific culture result being present.

Despite these antibiotics being used, although the urine was cleared of bacteria, the fever continued unabated!!

Hence, it was considered by the attending physicians that the fever was due to some other reason.

A series of computed tomography scans was engaged but they just confirmed the presence of congestive heart failure. The effusions were small and hence, it was difficult to attempt aspiration of those.

Echocardiogram was normal with no vegetation.

A senior physician was asked to help elucidate the cause of the fever and suggest treatment.

The attending physicians were unable to fathom why the CRP was negative despite the fever.

The senior doctor reviewed the history, physical and reviewed the laboratory data and scans.

It became clear that there were two urine analyses that showed a heavy presence of fungi. Moreover, the patient was diabetic with a catheter in situ.

It is not uncommon in the elderly to have fungal and bacterial contamination of the urine in chronically catheterised patients. However, when there are symptoms such as a fever and tachycardia, such contamination may actually be causing infection.

In this case, several broad spectrum antibiotics were used without resolution of the fever despite resolution of the bacterial infection.

It was suspected that the cause of the fever was a fungal urinary tract infection. Risk factors for this included being an elderly female, catherterised and being diabetic.

This type of problem is called antibiotic non-responsive infection and with fungi being present in the urine, and evidence of infection e.g. fever and tachycardia, such organisms should not merely be considered as contaminants.

The usual cause is candidal species and blood cultures are frequently unhelpful.

Treatment should include Fluconazole 200mg per day for 14 days or if non-responsive, due to resistance, Amphotericin B or 0.5mg per Kg for 7-14 days or Caspofungin.

The catheter should also be removed if possible.

In view that Fungal infection of the urinary tract can cause Bezoar formation and therefore cause obstruction, a search for such entities should be considered by ultrasound or CT of the urinary system and consideration of cystoscopy of the bladder.

In view of the digital clubbing, which can be caused by infective endocarditis, and because of the persistence of fever a repeat echocardiogram was advised.

The workup of a Fever of Unknown Origin can be difficult. Usually a good history and physical examination can provide several clues. However, in this case, no helpful history was obtainable and physical examination was not particularly revealing.

However, as with all FUOs, infection should always be ruled out first.
The longer a fever continues without an obvious source of infection being found, the less likely it is that it is an infectious cause, and therefore, no infectious causes should be considered.

Always remember that infections are not just bacterial. The can occur from viruses, fungi and protozoa as well. Laboratory results should always be compared to the patient's clinical presentation and whether such results are consistent with infection or not. Usually, the presence of fungi in the urine is of no consequence, but heavy colonisation, peristent fever and tachycardia despite antibiotics should raise the question of fungal UTI.

CRP- Cannot Rule out Pathology

The CRP was negative in this patient which proved to be an unhelpful test. CRP can certainly help guide investigation and treatment, but it is non-specific and can be negative in the elderly despite overwhelming sepsis. CRP is in my opinion, over used and overly relied upon by many physicians. It is more important to look at the patient than the CRP as the patient is the best model and when you treat a patient, you are not treating the CRP you must treat the patient.

CRP is predominantly a marker for inflammation/infection. It can be raised by many processes such as infection, malignancy, coronary artery disease and collagen vascular diseases. It shows that there is a problem but it is a non-specific marker. Reliance on non-specific tests can lead the physician into a false sense of security and lead to misdiagnosis. Absence of CRP does not mean that there is no problem and immune suppressed patients may not mount an appropriate response to an infective organism.

Broad Spectrum Antibiotics-- carBapenems Shall Avoid

The use of such broad spectrum antibiotics in this cause is also inappropriate. There are many other antibiotics that can be used for infection of the urinary tract that are very effective. The patient could have been given a penicillin drug such as amoxicillin-clavulanate or a second generation cephalosporin plus gentamicin initially rather than using a carbapenem. The problem with using carbapenems is inducing resistance. This should be avoided. Once there is resistance to the carbapenems, no penicillin/cephalosporin will work-- not a nice thought.

Use of fluoroquinolones is also another good option such as ciprofloxacin or levofloxacin. The use of Trimethoprim orally can also clear a bacterial infection and in fact, it is the antibiotic of choice for UTI by general practitioners and hospital physicians alike in uncomplicated urinary tract infections in the UK.

The fact that Vancomycin was used for potential MRSA urinary infection is a surprise. Vancomycin can indeed be used for urinary infections and sepsis syndromes, but MRSA UTI is not common and moreover, it had not been grown from the urine culture or blood cultures. It would seem suprising to find this and once again, going back to the patient, she looked well. Most patients with MRSA bacteraemia are very sick and in this case, MRSA would be less likely.

The take home message today is:

  • In patients with antibiotic non-responsive urinary infections, consider ruling out fungal infection. Remove urinary catheters if possible in fungal infection and consider a fuller examination of the whole urinary tract.
  • Try not to rely on CRP as it is a non-specific test; use your patient as a guide instead.
  • Use of antibiotics should be with combination of more traditional antibiotics first giving broad spectrum cover and then narrowing the spectrum once culture results are known. Try not to use the carbapenems as first line to reduce emergence of resistance. Use of Vancomycin should be considered in the context of the clinical situation e.g. is the patient sick? is the focus possible in the organ system you have identified? has MRSA been identified etc...

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